Adipose derived mesenchymal stem cells efficiently rescue carbon tetrachloride-induced acute liver failure in mouse.

BACKGROUND AND AIM: Adipose derived mesenchymal stem cells (ADMSCs) may be an attractive source for acute and chronic liver injury because they are abundant and easy to obtain. We aim to investigate the efficacy of ADMSCs transplantation in the acute liver failure (ALF) caused by carbon tetrachloride (CCl4) in mice. METHODS: ADMSCs were isolated from inguinal fat pads of enhanced green fluorescent protein (EGFP) transgenic mice and their surface markers and differentiation potential were analyzed. ALF models were established by infusion of CCl4 and divided into two groups: control group; EGFP-ADMSCs transplantation group. The restoration of biological functions of the livers receiving transplantation was assessed via a variety of approaches such as survival rates, live function parameters, histological localization of EGFP-ADMSCs, and Immunofluorescence analysis. RESULTS: ADMSCs were positive for CD105, CD44 but negative for CD45, CD34 and had adipogenic, osteogenic differentiation potential. The survival rate of transplantation group significantly increased compared to PBS group. Furthermore, the transplanted cells were well integrated into injured livers and produced albumin, cytokeratin-18. CONCLUSION: Direct transplantation of ADMSCs is an effective treatment for ALF. The transplanted ADMSCs exhibit the potential to differentiate into hepatocyte-like cells in the injured livers.

Hepatic stimulator substance alleviates toxin-induced and immune-mediated liver injury and fibrosis in rats.

BACKGROUND: Liver fibrosis is a common scarring response to chronic liver injury. It is a precursor to cirrhosis and liver carcinoma. Hepatic stimulator substance (HSS), a known liver-specific but species-nonspecific growth factor, has been shown to protect hepatocytes from various toxins. METHODS: We have investigated the effects of HSS therapy on carbon tetrachloride (CCl(4))-induced and porcine-serum-mediated hepatic injury and fibrosis. We hypothesize that HSS might attenuate liver injury and fibrosis by suppressing oxidative stress, down-regulating profibrogenic factors, and blocking HSCs activation. RESULTS: This report demonstrated that HSS therapy diminished α-smooth muscle actin expression, decreased intrahepatic reactive oxygen species (ROS) level, and down-regulated transforming growth factor (TGF)-ß1, platelet-derived growth factor (PDGF)-BB, and tissue inhibitor of metalloproteinase (TIMP)-1 expression. In addition, HSS treatment significantly protected the liver from injury by improving liver function tests and histological architecture of the liver. CONCLUSIONS: These results provided novel insights into the mechanisms of HSS in the protection of the liver. Our results suggested that HSS might be a therapeutic antifibrotic agent for the treatment of liver fibrosis.

Augmenter of liver regeneration (ALR) gene therapy attenuates CCl4-induced liver injury and fibrosis in rats.

Liver fibrosis represents a process of healing and scarring in response to chronic liver injury. Augmenter of liver regeneration (ALR) has been shown to protect hepatocytes from various toxins. The aim of this study was to investigate the effects of ALR gene therapy on liver injury and fibrosis induced by CCl(4) in rats and further explore the underlying mechanisms. Human ALR expression plasmid was delivered via the tail vein. ALR gene therapy might protect the liver from CCl(4)-induced injury and fibrogenesis by attenuating the mitochondrial dysfunction, suppressing oxidative stress, and inhibiting activation of HSCs. This report demonstrated that ALR gene therapy protected against the ATP loss, increased the activity of ATPase, decreased intrahepatic reactive oxygen species level, and down-regulated transforming growth factor-ß1, platelet-derived growth factor-BB, and α-smooth muscle actin expression. Following gene transfer liver function tests were significantly improved. In brief, ALR gene therapy might be an effective therapeutic reagent for liver fibrosis with potential clinical applications.

[The cloning of human augmentor of liver regeneration-interacting proteins].

AIM: To screen human augmentor of liver regeneration(hALR)-interacting proteins and to explore the mechanisms of hALR in liver regeneration. METHODS: The open reading frame of hALR was used to construct the "bait" plasmid and the genes encoding hALR-interacting proteins were screened from the human liver cDNA library that was pretransformed into yeast Y187 by yeast two-hybrid system. Bioinformatic analysis of the sequences of the positive clones were performed. RESULTS: The positive clones encoding metallothionein, albumin, selenoprotein P,Na/K-ATPase, and 2 unknown proteins were screened out. CONCLUSION: The successful cloning of the genes encoding proteins interacting with hALR may pave the way for studying the interaction between the above proteins and hALR, and the molecular mechanisms of biological effect of hALR.

[Infectious distribution and resistant of Neisseria gonorrhoeae, Mycoplasma, and Chlamydia trachomatis in the chronic prostatitis].

OBJECTIVE: To investigate the infectious distribution and resistant of Neisseria gonorrhoeae, Mycoplasma, and Chlamydia trachomatis in the chronic prostatitis. METHODS: The identification and susceptibility of Neisseria gonorrhoeaes and Mycoplasmas were detected by a cultural method. The nitrocefin test was used to detect the beta-lactamase in Neisseria gonorrhoeae strains. Chlamydia trachomatis was identificated by a monoclonal gold labeled antibody method. RESULTS: A total of 2,900 prostatic fluids were detected and the rates of isolation of Neisseria gonorrhoeae, Mycoplasma, and Chlamydia trachomatis were 3.3%, 12.8%, and 0.9%, respectively. The prevalence of beta-lactamase in Neisseria gonorrhoeae strains was 12.6%. The resistant percentages of Neisseria gonorrhoeae strains were 73.7% to penicillin and 91.6% to ciprofloxacin and ofloxacin respectively, but the susceptibility to spectinomycin, cephalosporin and cefoxitin was good. The resistant rates of Mycoplasma to tetracycline, acetylspiramycin, erythromycin, and ofloxacin were 50.0% or more, but the susceptibilities to roxithromycin, doxycyclin, levofloxacin, minocyclin, josamycin, and azithromycin were about 70.0%-80.0%. CONCLUSION: The isolation rate of Mycoplasma is higher than that of Neisseria gonorrhoeae and Chlamydia trachomatis in the chronic prostatitis. It is important to detect the susceptibility of Neisseria gonorrhoeae and Mycoplasma for the use of antibiotics in reason.

[Extended-spectrum beta-lactamase detection in Enterobacteriaceae and antibiotic susceptibility analysis].

OBJECTIVE: To detect the extended-spectrum beta-lactamases (ESBLs) in family Enterobacteriaceae and analyze the antibiotic susceptibility of those ESBLs-producing strains. METHODS: ESBLs were determined by the double-disk confirmatory test and 8 antibiotic susceptibilities were tested with the disk disffusion method in those strains producing ESBLs. RESULTS: Forty-seven ESBLs-producing strains comprised of 25 of E. coli, 14 of K. pneumoniae, 5 of E. cloacae, 1 of K. oxytoca, 1 of K. rhinoscleromatis, and 1 of S. liquefaciens. The susceptibility rates of those strains were: 100% for imipenem and meropenem, 89.4% for piperacillin/tazobactam, 72.4% for cefoxitin and 65.9% for cefotetan. CONCLUSION: E. coli and K. pneumoniae are the prime strains producing ESBLs in Enterobacteriaceae. Imipenem and meropenem are the best drugs to deal with those ESBLs-producing strains. Piperacillin/tazobactam is better than cephamycins and other beta-lactama/beta-lactamase inhibitor combination.